Overall, aspirin users had a 38% reduced risk of colorectal and other gastrointestinal cancers compared with nonusers. Mortality risk was 15% lower and metastasis was 35% to 40% lower among regular aspirin users.

Aspirin use also reduced risk for major vascular events, but these benefits were initially offset by an increased risk for major bleeding events. Both of these affects diminished over time, however, leaving only a reduced risk for cancer after three years, Peter M. Rothwell, FMedSci, of the University of Oxford in England, and colleagues reported in three studies published online in Lancet and Lancet Oncology.

"In view of the very low rates of vascular events in recent and ongoing trials of aspirin in primary prevention, prevention of cancer could become the main justification for aspirin use in this setting, although more research is required to identify which individuals are likely to benefit most," they wrote.

In an accompanying editorial, Andrew T. Chan, MD, and Nancy R. Cook, ScD, of Harvard and Brigham and Women's Hospital in Boston, acknowledged that although the findings were promising, there were several limitations to the studies.

The analyses did not include data from the two largest clinical evaluations of aspirin's effect on cancer risk – the Women's Health Initiative and the Physicians' Health Study – which involved more than 60,000 men and women, neither of which demonstrated aspirin affected cancer risk.

Furthermore, Chan and Cook pointed out that aspirin-associated bleeding or anemia may have resulted in earlier diagnosis and removal of cancers, leading to a possible alternative explanation for the study findings.

"These caveats notwithstanding, Rothwell and colleagues show quite convincingly that aspirin seems to reduce cancer incidence and death across different subgroups and cancer sites, with an apparent delayed effect," they concluded, adding that the risk-benefit profile seems to favor long-term anticancer benefits.

The three articles described cancer-related health outcomes among more than 200 randomized, cohort and case control studies, involving various analyses performed among millions of participants. Mortality assessment alone involved 51 trials and included more than 100,000 patients.

Results from the principle analysis, which included 34 trials and 69,224 participants, showed a 0.85 mortality odds ratio in favor of aspirin (P=0.008). This benefit increased to a 37% reduced risk for cancer mortality from five years onwards (OR= 0.63; P=0.0005).

The analysis that examined aspirin's affect on metastasis included five randomized trial and followed 17,285 study participants for an average of 6.5 years. Overall, patients assigned to aspirin had a 36% reduced risk of distant metastasis (P=0.001), and a 46% reduced risk for metastatic adenocarcinoma (P=0.0007), including colon, lung and prostate cancers.

The third study involved a systematic review and meta-analysis of cohort and case-control studies published from 1950 to 2011 that were stratified by frequency, dose and duration of aspirin use. Results from observational studies were compared with results from randomized controlled trials.

Data from the case-control studies indicated that regular aspirin use reduced the risk of colorectal cancer 38% (OR=0.62; P<0.0001). Similar results were observed for other gastrointestinal cancers, including esophageal, gastric and biliary, as well as breast cancer.

After adjusting for baseline characteristics, cancer stage, and duration and frequency of aspirin use, cohort study data indicated regular use of aspirin was associated with 31% fewer cancers with distant metastases (OR=0.98). However, regular use did not seem to affect regional spread.

"Observational studies show that regular use of aspirin reduces the long-term risk of several cancers and the risk of distant metastasis. Results of methodologically rigorous studies are consistent with those obtained from randomized controlled trials, but sensitivity is particularly dependent on appropriately detailed recording and analysis of aspirin use," the researchers noted.

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